Minimum alveolar concentrations (MAC) of halothane, enflurane, and isoflurane in ferrets

The minimum alveolar concentrations (MAC) of isoflurane, enflurane, and halothane were determined in adult male ferrets during controlled ventilation at normothermia (37 degrees C). Mean (+/- SD) MAC values for isoflurane (n = 8), enflurane (n = 8), and halothane (n = 8) at 37 degrees C were 1.52 +/- 0.10%, 1.99 +/- 0.18%, and 1.01 +/- 0.10%, respectively. Halothane MAC was reduced by 26% in the presence of 70% N2O. At 29.9 +/- 0.2 degrees C, the mean MAC value of halothane (0.85 +/- 0.11%) was 16% less than MAC at 37 degrees C. The relative potencies of the halogenated anesthetics are of the same order as those reported for large animals and for humans.     

Plasma Inorganic Fluoride Concentrations after Sevoflurane Anesthesia in Children

Background: Sevoflurane is degraded in vivo in adults yielding plasma concentrations of inorganic fluoride [Fluorine sup -] that, in some patients, approach or exceed the 50-micro Meter theoretical threshold for nephrotoxicity. To determine whether the plasma concentration of inorganic fluoride [Fluorine sup -] after 1-5 MAC *symbol* h sevoflurane approaches a similar concentration in children, the following study in 120 children scheduled for elective surgery was undertaken.

Methods: Children were randomly assigned to one of three treatment groups before induction of anesthesia: group 1 received sevoflurane in air/oxygen 30% (n = 40), group 2 received sevoflurane in 70% N2 O/30% O2 (n = 40), and group 3 received halothane in 70% N2 O/30% O sub 2 (n = 40). Mapleson D or F circuits with fresh gas flows between 3 and 6 l/min were used. Whole blood was collected at induction and termination of anesthesia and at 1, 4, 6, 12, and 18 or 24 h postoperatively for determination of the [Fluorine sup -]. Plasma urea and creatinine concentrations were determined at induction of anesthesia and 18 or 24 h postoperatively.

Results: The mean (+/-SD) duration of sevoflurane anesthesia, 2.7+/-1.6 MAC *symbol* h (range 1.1-8.9 MAC *symbol* h), was similar to that of halothane, 2.5+/-1.1 MAC *symbol* h. The peak [Fluorine sup -] after sevoflurane was recorded at 1 h after termination of the anesthetic in all but three children (whose peak values were recorded between 4 and 6 h postanesthesia). The mean peak [Fluorine sup -] after sevoflurane was 15.8+/-4.6 micro Meter. The [Fluorine sup -] decreased to < 6.2 micro Meter by 24 h postanesthesia. Both the peak [Fluorine sup -] (r2 = 0.50) and the area under the plasma concentration of inorganic fluoride-time curve (r2 = 0.57) increased in parallel with the MAC *symbol* h of sevoflurane. The peak [Fluorine sup -] after halothane, 2.0+/-1.2 micro Meter, was significantly less than that after sevoflurane (P < 0.0001) and did not correlate with the duration of halothane anesthesia (MAC *symbol* h; r2 = 0.007). Plasma urea concentrations decreased 24 h after surgery compared with preoperative values for both anesthetics (P < 0.01), whereas plasma creatinine concentrations did not change significantly with either anesthetic.     

Minimum alveolar concentration of halothanediethyl-ether azeotrope

The azeotropic mixture of halothane and diethyl ether (HE) may be a valuable alternative to other anaesthetic agents under circumstances such as war, civil disaster, and primitive conditions. In the present study the minimum alveolar concentrations (MACs) for HE in man (n = 25) and in pigs (n = 6) were determined. For comparison with results of other studies, the MAC for halothane in man (n = 14) was also determined. A Normac gas analyser and a Varian 3700 gas chromatograph were calibrated against known standards of HE. The performance of two vaporizers (Fluotec Mark III, Servo vaporizer for halothane) was studied. The Fluotec Mark III vaporizer and the Servo halothane vaporizer filled with HE gave a linear performance with increasing dial settings. The Normac gas analyser set for methoxyflurane was linearly sensitive to the ether component of the azeotrope. The MAC for HE in man was 0.71 vol.% +/- 0.03 (s.e.mean) (ether 0.21 vol.%, halothane 0.50 vol.%) in the age group 19-42 years. MAC for halothane in man was 0.65 +/- 0.03 in the age group 19-32 years. The MAC for HE in pigs between 20-24 kg was 0.99 vol.% +/- 0.07. The ether component seems to act synergistically with halothane in the azeotropic mixture. The present study provides an opportunity to compare HE with other volatile anaesthetic agents.     

Nitrous oxide in combination anesthesia. Quantitative aspects of the effect of nitrous oxide

Minimal Alveolar Concentration (MAC) defines the anesthetic potency of nitrous oxide (N2O) combined with an inhalational anesthetic only for the moment of skin incision. For the complete operation, the proportional action of N2O is unknown. This prospective, randomized study reports the mean intraoperative concentration (MIC) of halothane with and without 70% N2O in combination with premedication, i.v. induction, and muscle relaxation for the duration of operation. METHODS: Forty ASA I-II patients scheduled for hysterectomies gave informed consent. All patients received atropine 0.5 mg, promethazine and pethidine 1 mg/kg i.m. 30-45 min prior to anesthesia, i.v. induction with thiopental, and neuromuscular blockade with alcuronium at the beginning of the operation. Post-induction, patients received randomized halothane in 30% O2/70% N2 (group 1, n = 20) or in 30% O2/70% N2O (group 2, n = 20). In the course of this observation (before induction and up to 15 min after extubation), the following parameters were measured (Table 1): arterial pressure (AP), heart rate (HR), plasma concentrations of growth hormone, prolactin, and cortisol in central venous blood, esophageal temperature, "train-of-four" ratio, and expiratory CO2 concentration. MIC had been computed from the integral of end-expiratory halothane concentration during the course of the operation. RESULTS: Biometric data and concomitant conditions were equivalent within the two groups (Table 2). MIC halothane was 0.72 +/- 0.014 vol% in group 1 (O2/N2) and 0.52 +/- 0.01 vol% in group 2 (O2/N2O).(ABSTRACT TRUNCATED AT 250 WORDS)     

Respiratory effects of nitrous oxide during halothane or enflurane anaesthesia in children

The respiratory effects of nitrous oxide (N2O) were studied during halothane and enflurane anaesthesia in 12 children (mean age 46.4 +/- 29.3 months, mean weight 15.3 +/- 4.2 kg) during surgery under continuous extradural anaesthesia. Four equipotent anaesthetic states were studied in random order: 1) halothane 1 MAC in oxygen, 2) halothane 0.5 MAC + 50% N2O, 3) enflurane 1 MAC in oxygen, 4) enflurane 0.5 MAC +50% N2O. End-tidal fractions of CO2 (PetCO2) and halothane and enflurane were measured using infrared analysers. The respiratory variables (tidal volume VT, minute ventilation VE, respiratory frequency F, inspiratory time Ti, mean inspiratory flow VI, effective inspiratory time Ti/Ttot) were measured using a pneumotachograph. Significant changes were observed between the four states for VE, VI, F and PetCO2, whereas the values of VT, Ti and Ti/Tot did not differ significantly. The respiratory depressant effect of 1 MAC of either halothane alone or of the mixture of halothane and N2O was very similar. During enflurane anaesthesia, PetCO2 was less increased when N2O was substituted for enflurane, owing to a significant increase in respiratory frequency. A marked decrease in VE together with an increase in PetCO2 was observed during enflurane anaesthesia (states 3 and 4) when compared to the corresponding states during halothane anaesthesia (states 1 and 2). The respiratory depressant effect of enflurane is greater than that of halothane in unpremedicated children, even when substituting N2O for an equal MAC fraction of enflurane.2+ The effect of N2O on respiratory patterns seems to depend on the inhalational agent used and/or on the vesting respiratory frequency.     

Hemodynamic responses to nitrous oxide during inhalation anesthesia in pediatric patients

STUDY OBJECTIVE: To measure the hemodynamic changes produced by nitrous oxide (N2O) during halothane and isoflurane anesthesia in infants and children. DESIGN: A repeated measures design in two groups of infants and small children. SETTING: Operating rooms at a university hospital. PATIENTS: Nineteen healthy unmedicated infants and small children (mean age 12 months) who required elective surgery. INTERVENTIONS: Prior to anesthesia induction, cardiovascular measurements were recorded using pulsed Doppler and two-dimensional echocardiography. Following anesthesia induction with halothane (n = 10) or isoflurane (n = 9) in oxygen (O2) and air, anesthetic measures were stabilized at 1.0 minimum alveolar concentration (MAC) and cardiovascular measures were repeated. After 30% N2O was added to the 1.0 MAC anesthetic concentration, a third set of cardiovascular measurements was recorded. A final cardiovascular data set was measured 5 minutes following an increase in N2O concentration to 60%. MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure (MAP), cardiac index (CI), stroke volume (SV), and ejection fraction (EF) decreased similarly and significantly at 1.0 MAC halothane and isoflurane. Heart rate (HR) increased during isoflurane anesthesia but decreased during halothane anesthesia. The addition of N2O resulted in a decrease in HR, CI, and MAP when compared to 1.0 MAC levels of halothane or isoflurane; however, SV and EF were not significantly changed from levels measured during 1.0 MAC halothane or isoflurane. CONCLUSIONS: The addition of N2O to halothane and isoflurane anesthesia in infants and children decreased HR. This decrease led to a decrease in cardiac output (CO). Unlike with adults, N2O did not produce cardiovascular signs of sympathetic stimulation in infants and children.     

Comparative hemodynamic depression of halothane versus isoflurane in neonates and infants: an echocardiographic study.

The purpose of this study was to measure and compare the relationship of cardiovascular depression and dose during equal potent levels of halothane and isoflurane anesthesia in neonates (n = 19) (16.7 +/- 6.9 days) and infants (n = 54) (6.1 +/- 3.1 mo). Seventy-three children had heart rate, arterial blood pressure, and pulsed Doppler pulmonary blood flow velocity as well as two-dimensional echocardiographic assessments of left ventricular area and length recorded just before anesthesia induction. Anesthesia was induced by inhalation of increasing inspired concentrations of halothane or isoflurane in oxygen using a pediatric circle system and mask. During controlled ventilation, halothane and isoflurane concentrations were adjusted to maintain 1.0 MAC and then 1.5 MAC (corrected for age), and echocardiographic and hemodynamic measurements were repeated. A final cardiovascular measurement was recorded after intravenous administration of 0.02 mg/kg of atropine. All measurements were completed before tracheal intubation and the start of elective surgery. In neonates, 1.0 MAC concentrations of halothane and isoflurane decreased cardiac output (74% +/- 16%), stroke volume (75% +/- 15%), and ejection fraction (76% +/- 15%) similarly from awake levels. Decreases in cardiac output, stroke volume, and ejection fraction with halothane and isoflurane were significantly larger at 1.5 MAC (approximately 35% decreases from awake values) than at 1.0 MAC. Heart rate decreased significantly during 1.5 MAC halothane anesthesia (94% +/- 4%) but remained unchanged during isoflurane anesthesia. In infants, 1.0 MAC halothane and isoflurane decreased cardiac output (83% +/- 12%), stroke volume (78% +/- 12%), and ejection fraction (74% +/- 12%) when compared with awake measures.(ABSTRACT TRUNCATED AT 250 WORDS)     

Atracurium, vecuronium, and pancuronium do not alter the minimum alveolar concentration of halothane in humans

The authors studied 64 unpremedicated, healthy surgical patients, aged 42 +/- 14 yr, to determine the effects of atracurium, vecuronium, and pancuronium on the minimum alveolar concentration (MAC) of halothane. Anesthesia was induced using halothane/nitrous oxide/oxygen via a mask without the administration of other drugs. Nitrous oxide was discontinued, the trachea was intubated without prior administration of neuromuscular blocking drugs, and anesthesia was maintained with halothane in oxygen. Participating patients were assigned to one of five groups: 1) no neuromuscular blocking drug (control group, n = 9); 2) atracurium 0.5 mg/kg (n = 10); 3) atracurium 1.0 mg/kg (n = 15); 4) vecuronium 0.1 mg/kg (n = 20); or, 5) pancuronium 0.1 mg/kg (n = 10). Tourniquets, inflated to 300 mmHg immediately before iv administration of neuromuscular blocking drug and 15-30 min prior to skin incision, were used to isolate extremities from circulating neuromuscular blocking drug in all patients. A positive response to stimulation was defined as movement of at least one extremity occurring distal to the tourniquet within 1 min following skin incision. The first patients in the control and atracurium groups were studied at an end-tidal halothane concentration of 0.95%. The first patient in the pancuronium group was studied at a halothane concentration of 0.75%, and the first patient in the vecuronium group at 0.70%. Subsequent patients were studied at end-tidal halothane concentrations 0.10% above or below that of the preceding patient, depending on the presence or absence of movement with skin incision. Control MAC for halothane was 0.74% +/- 0.09% (mean +/- SEM).(ABSTRACT TRUNCATED AT 250 WORDS)     

Halothane concentrations required to block the cardiovascular responses to incision (MAC CVR) in infants and children

The purpose of this study was to determine the halothane concentration in N₂O required to block the cardiovascular responses to skin incision (MAC CVR) in infants and children. We studied 64 unpremedicated ASA 1 infants and children (one month to seven years). In each infant or child, anaesthesia was induced slowly with halothane and N₂O, and an endotracheal tube was placed. The MAC CVR was assessed, after a steady state end-tidal halothane concentration had been established for ten minutes, by the “up and down technique” of Dixon. Positive responses were defined as an increase in MAP or HR > 10%. The MAC CVR50 values of halothane with 60% N₂O were 1.16 ± 0.23% at 1–6 mo, 1.17 ± 0.18% at 7–12 mo, 0.95 ± 0.26% at 1–3 yr, and 1.12 ± 0.16% at 4–7 yr. The value at 1–3 years children was less than those in the other age groups (P < 0.05). The changes of MAP were correlated with changes of both HR and pupillary diameter. These results indicate that the values of MAC CVR50 of halothane in infants and children are higher than those required to block motor responses (MAC). The halothane requirement to block cardiovascular responses is lowest in the children aged one to three years.     

EEG changes during carotid occlusion and hypotension in the rat: the effects of nitrous oxide

It has been suggested that N2O may alter the sensitivity of the brain to ischemia. To test this hypothesis. we examined the effects of N2O on the development of left-right hemispheric asymmetry in the electroencephalogram (EEG) during hemorrhagic hypotension in rats subjected to unilateral carotid occlusion. Rats were anesthetized with halothane/O2/air, and ventilated to normocarbia (PaCO2 approximately 40 mm Hg). Catheters were placed in the femoral artery and vein, and both common carotid arteries (CCA) were exposed. Bilateral fronto-occipital screws were then placed to record left and right hemispheric EEGs, which were processed by computer and stored on disc. Animals were then randomly assigned to one of three treatment groups (n = 8 each): group 1, 0.5 MAC (0.5%) halothane + 0.5 MAC (70%) N2O; group 2, 1 MAC (1.0%) halothane + 70% nitrogen; and group 3, 1 MAC halothane + 70% N2O. After stabilization, the left CCA were occluded. Animals with EEG changes at this point were discarded. Beginning 5 min later, venous blood withdrawal was started at a rate of 0.25 ml/min, while mean arterial blood pressure (MAP) and EEG were continuously recorded. After exsanguination was complete, EEG data (raw and processed) were re-examined by an individual who was unaware of the anesthetics administered to determine the MAP at which any evidence of EEG asymmetry appeared. There were no intergroup differences in weight, PaO2, PaCO2, pHa, blood glucose. hematocrit, or starting (prebleed) MAP. The earliest change in the EEG was typically a decrease in total amplitude over the hemisphere ipsilateral to the carotid occlusion. Adding 70% N2O to a 1 MAC halothane background (group 2 vs. group 3) had no effect on the MAP at which this EEG asymmetry appeared (54 +/- 13 vs. 53 +/- 10 mm Hg). However, this MAP was significantly higher in animals breathing 0.5 MAC halothane + 0.5 MAC N2O (group 1, 78 +/- 17 mm Hg, p = 0.0019 by ANOVA). We conclude that 70% N2O had no direct effects on the MAP at which EEG abnormalities appear (group 2 vs. 3), and that the observed differences are more closely related to the concentration of volatile agent. Whether these differences are related to anesthetic-induced differences in the brain's tolerance to reduced CBF or whether there are differences in cerebral blood flow (CBF) autoregulation are unknown.     

The effect of nitrous oxide on cortical cerebral blood flow during anesthesia with halothane and isoflurane, with and without morphine, in the rabbit

The effect of nitrous oxide on cortical cerebral blood flow (CBF) was examined during a varying background anesthetic state in the New Zealand White rabbit. Seventy percent nitrous oxide resulted in significant and similar increases in CBF during anesthesia with both 0.5 MAC of halothane (44 +/- 14 to 63 +/- 17 ml.100 g-1.min-1) (mean +/- SD) and anesthesia with isoflurane (34 +/- 9 to 41 +/- 11 ml.100 g-1.min-1). During anesthesia with 1.0 MAC halothane or isoflurane, N2O also increased CBF, but the increments (halothane, 73 +/- 34 to 111 +/- 54 ml.100 g-1 min-1; isoflurane 34 +/- 13 to 69 +/- 34 ml.100 g-1.min-1) were significantly greater than those observed at 0.5 MAC. When 0.5 MAC halothane or isoflurane was supplemented with morphine (10 mg/kg followed by an infusion of 2 mg.kg-1.min-1), the CBF effect of N2O was not significantly different from that observed with 0.5 MAC alone. It was concluded that, in the rabbit, the effects of N2O on cortical CBF vary with the background anesthetic state and that the increase in CBF caused by N2O becomes greater as the end-tidal concentration of halothane or isoflurane increases from 0.5 to 1.0 MAC. Morphine, when added to 0.5 MAC of halothane or isoflurane, does not alter the effect of 70% N2O on cortical CBF.     

Xenon suppresses the hypnotic arousal in response to surgical stimulation.

STUDY OBJECTIVE: To evaluate the suppressive effects of xenon (Xe) on hypnotic arousal at skin incision. DESIGN: Prospective, randomized study. SETTING: Operating rooms at a university hospital. PATIENTS: 35 ASA physical status I and II patients presenting for elective lower abdominal surgery. INTERVENTIONS: Patients were randomly assigned to receive one of the following regimens: 1.3 minimum alveolar concentration (MAC) isoflurane, 1.3 MAC sevoflurane, 0.7 MAC Xe with 0.6 MAC sevoflurane, 1 MAC Xe with 0.3 MAC sevoflurane, or 0.7 MAC nitrous oxide (N2O) with 0.6 MAC sevoflurane (n = 7 each group). MEASUREMENTS AND MAIN RESULTS: The bispectral index (BIS) was measured at baseline, during anesthesia, and after skin incision. BIS increased significantly at skin incision from the values noted during anesthesia in the sevoflurane and N2O groups, whereas it remained stable at incision in the other three groups (mean change in BIS: 0 +/- 9 for isoflurane, 15 +/- 8 for sevoflurane, 5 +/- 6 for 0.7 MAC Xe, 4 +/- 11 for 1 MAC Xe, and 9 +/- 5 for N2O). CONCLUSIONS: Unlike N2O, Xe was able to suppress hypnotic arousal in response to surgical stimulation when administered with sevoflurane.     

Mivacurium infusion requirement and spontaneous recovery of neuromuscular transmission in children anaesthetized with nitrous oxide and fentanyl,halothane, isoflurane or sevoflurane

BACKGROUND: Forty children, aged 3-11 years, ASA I or II, were allocated at random to receive N2O/O2-fentanyl or 1 MAC halothane, isoflurane or sevoflurane-N2O/O2 anaesthesia. Mivacurium was used for muscle relaxation. METHODS: Electromyographic response of the adductor pollicis to train-of-four (TOF) stimulation, 2 Hz for 2 s, applied to the ulnar nerve at 10-s intervals was recorded using the Relaxograph (Datex, Helsinki, Finland). An intubating dose of mivacurium, 0.2 mg.kg-1 was given, and when T1 returned to 5%, muscle relaxation was maintained by continuous infusion of mivacurium, adjusted manually to maintain a stable 90-99% block. RESULTS: Halothane, isoflurane and sevoflurane groups had lower infusion requirements for mivacurium than the N2O-fentanyl group (P=0.000083). Mivacurium requirement was 18.8 +/- 6.8, 10.8 +/- 4.2, 6.9 +/- 3.9 and 9.6 +/- 5.6 microg.kg-1.min-1 for children receiving N2O/O2-fentanyl, halothane, isoflurane and sevoflurane anaesthesia, respectively. CONCLUSIONS: Spontaneous recovery from T1=10% to TOF ratio=0.7 was insignificantly prolonged from 6.3 to 12.5 min in the fentanyl group to 7-16.5 min in children anaesthetized with inhalational anaesthetics.     

Effect of chloride transport blockade on the MAC of halothane in the rat.

There is a growing evidence that central nervous system chloride transport via gamma-aminobutyric acid (GABAA) related Cl- conductance or Cl-/HCO3- exchange affects anesthetic requirements. To delineate the effects of GABAA-related Cl- conductance blockade versus Cl-/HCO3- exchange inhibition, we determined the change in minimum alveolar anesthetic concentration (MAC) of halothane in rats after intracisternal infusion of 4,4'-diisothiocyano-2,2'-disulfonic acid stilbene (DIDS). DIDS inhibits Cl-/HCO3- exchange transport in concentrations greater than 1 microM and in GABAA-related Cl- channels in concentrations greater than 0.1 mM. After control MAC determination, rats were given intracisternal mock cerebrospinal fluid (n = 6), 1.0 microM DIDS (n = 8), or 1 mM DIDS (n = 8) at a rate of 2 microL/min for 30 min. Mock cerebrospinal fluid did not change the MAC of halothane. The MAC of halothane increased significantly (P less than 0.001) from 0.96% +/- 0.02% to 1.11% +/- 0.03% (mean value +/- SEM) with 1 microM DIDS and from 0.94% +/- 0.02% to 1.16% +/- 0.04% with 1 mM DIDS. The increases in MAC with 1 microM and 1 mM DIDS were not statistically different. This suggests that Cl-/HCO3- exchange inhibition increases halothane requirements, whereas GABAA-related Cl- channel blockade does not.     

The anticonvulsant effects of volatile anesthetics on lidocaine-induced seizures in cats

Large concentrations of sevoflurane and isoflurane, but not halothane, induce spikes in the electroencephalogram. To elucidate whether these proconvulsant effects affect lidocaine-induced seizures, we compared the effects of sevoflurane, isoflurane, and halothane in cats. Fifty animals were allocated to 1 of 10 groups: 70% nitrous oxide (N2O), 0.6 minimum alveolar anesthetic concentration (MAC) + 70% N2O, 1.5 MAC + 70% N2O, and 1.5 MAC of each volatile agent in oxygen. Lidocaine 4 mg x kg(-1) x min(-1) was infused IV under mechanical ventilation with muscle relaxation. Electroencephalogram in the cortex, amygdala, and hippocampus and multiunit activities in the midbrain reticular formation (R-MUA) were recorded. Lidocaine induced spikes first from the amygdala or hippocampus in the 70% N2O and halothane groups and from the cortex in the sevoflurane and isoflurane groups. Lidocaine induced seizures in all cats in the 70% N2O and 0.6 MAC + N2O groups. Seizure occurrence was reduced in the 1.5 MAC + N2O group (P < 0.05 versus 70% N2O). The onset of seizure was delayed in the 0.6 MAC + N2O and 1.5 MAC groups for sevoflurane and isoflurane, but not for halothane, compared with the 70% N2O group (P < 0.05). Lidocaine increased R-MUA with seizure by 130%+/-56% in the 70% N2O group. The increase of R-MUA with seizure was more suppressed in the volatile anesthetic groups than in the 70% N2O group (P < 0.05). In the present study, sevoflurane and isoflurane attenuated seizure when the blood lidocaine concentration was accidentally increased. IMPLICATIONS: Increasingly, epidural blockade is combined with general anesthesia to achieve stress-free anesthesia and continuous pain relief in the postoperative period. In the present study, sevoflurane and isoflurane attenuated seizure when the blood lidocaine concentration was accidentally increased.     

Adenosine decreases the minimum alveolar concentration of halothane in dogs

Adenosine has sedative properties, and adenosine-receptor agonists have been found to reduce anesthetic requirements in rodents. This study determined whether adenosine, in hypotensive doses, reduces anesthetic requirements in halothane-anesthetized dogs. In seven animals, minimum alveolar concentration (MAC) for halothane was determined by a tail-clamp technique at three time points: after 2 h of halothane anesthesia, during adenosine-induced hypotension (mean arterial pressure: 55 mmHg), and 1 h after adenosine was discontinued. In other dogs, the effects of aminophylline, dipyridamole, or the specific adenosine-receptor antagonist 8-phenyl-theophylline (8-PT) on the halothane-adenosine interaction were studied. Adenosine significantly reduced halothane MAC, by 49%, from 0.76 +/- 0.05 to 0.39 +/- 0.05 vol% (mean +/- SEM). This effect was blocked by the concurrent administration of aminophylline (n = 5, P less than 0.05) or 8-PT (n = 4 of 4). When dipyridamole, which increases the plasma concentrations of endogenous adenosine, was administered alone, halothane MAC was reduced from 0.79 +/- 0.03 to 0.67 +/- 0.05 vol% (n = 5, P = 0.09). We conclude that exogenous adenosine substantially reduces halothane MAC in dogs and that this effect is blocked by the concurrent administration of the adenosine-receptor antagonists aminophylline or 8-PT. Relatively small alterations of endogenous adenosine concentrations, however, do not substantially reduce halothane MAC.     

Pulsed Doppler and two-dimensional echocardiography: comparison of halothane and isoflurane on cardiac function in infants and small children

The combination of two-dimensional and pulsed Doppler echocardiography was used to measure determinants of cardiac function in 20 ASA physical status I infants and small children (9 days-32 months of age) during equipotent halothane (n = 10) or isoflurane (n = 10) anesthesia in oxygen. Five sets of cardiovascular data were recorded in each patient. In the awake, unmedicated state prior to induction, at three different anesthetic levels, 0.75, 1.0, and 1.25 MAC (corrected for age) and a final measurement repeated at 1.25 MAC after the intravenous infusion of 15 ml X kg-1 of Lactated Ringers solution. The study was completed prior to intubation and surgery. Results are expressed as mean +/- SEM. Isoflurane and halothane decreased mean blood pressure from the awake level (isoflurane 76.6 +/- 2.3 to 60.6 +/- 3.1 mm, halothane 72.2 +/- 3.9 to 60.6 +/- 3.1 mm at 1.25 MAC). Isoflurane increased heart rate at all anesthetic levels (128.7 +/- 4.2 to 142.5 +/- 6.0 beats/min at 0.75 MAC). Halothane decreased heart rate at 1.25 MAC (124.6 +/- 4.6 to 119.4 +/- 3.5 beats/min). Isoflurane and halothane decreased cardiac index at 1.25 MAC. Stroke volume index decreased at 1.0 and 1.25 MAC with both isoflurane (36.9 +/- 3.8 to 30.2 +/- 3.5 ml/m2) and halothane (32.7 +/- 2.5 to 28.9 +/- 2.5 ml/m2). Ejection fractions also decreased significantly at 1.0 and 1.25 MAC in both groups of patients (22 +/- 6% at 1.25 MAC halothane and 28 +/- 8% at 1.25 MAC isoflurane).(ABSTRACT TRUNCATED AT 250 WORDS)     

Depression of ventilation by desflurane in humans

We studied the ventilatory effects of desflurane (formerly I-653) with and without N2O in healthy male volunteers. After insertion of venous and arterial (radial and pulmonary) catheters, baseline measurements of tidal volume (VT), respiratory rate (RR), ventilatory response to CO2, and arterial and mixed venous blood gases were made. Subjects were randomly assigned to receive either desflurane with O2 (n = 6) or with O2 and 60% N2O (n = 6). Anesthesia was induced by inhalation of desflurane followed by tracheal intubation without muscle relaxants. In each volunteer, at end-tidal concentrations totaling 0.83, 1.24, and 1.66 MAC, we repeated measurements of VT, RR, response to CO2, and arterial and mixed venous blood gases. As depth of anesthesia increased, VT significantly (P less than 0.05) decreased from 363 +/- 22 ml awake to 76 +/- 22 ml at 1.66 MAC without N2O and from 473 +/- 70 ml awake to 128 +/- 6 ml at 1.66 MAC with N2O (mean +/- SE). Similarly, RR increased from 15 +/- 0.5 breaths per min awake to 32 +/- 2 breaths per min at 1.66 MAC without N2O and from 14 +/- 0.5 breaths per min awake to 40 +/- 3 breaths per min at 1.66 MAC with N2O. Desflurane without N2O depressed the ventilatory response to CO2 to 45 +/- 9, 31 +/- 5, and 11 +/- 4% of the awake values at 0.83, 1.24, and 1.66 MAC, respectively. With N2O, values were 52 +/- 14, 23 +/- 5, and 26 +/- 9% of the awake value at 0.83, 1.24, and 1.66 MAC, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Neuromuscular and cardiovascular effects of mivacurium in children

The neuromuscular and cardiovascular effects of mivacurium chloride (BW B1090U) were evaluated in 90 children (2-12 yr) during N2O:O2 halothane or N2O:O2 narcotic anesthesia. Neuromuscular response was evaluated by recording the force of contraction of the adductor of the thumb during train-of-four stimulation at 0.1 Hz. The children were divided into two groups. Patients in group A (n = 45) were anesthetized with N2O:O2 and halothane (1% inspired) and patients in group B (n = 45) were anesthetized with N2O:O2 and fentanyl or morphine. Each group was further divided into five subgroups of nine children. Children in the first three sets of subgroups (A1-A3, B1-B3) received an initial dose of 0.02, 0.04, 0.05, 0.06 or 0.07 mg/kg mivacurium to determine dose response relationships under the different anesthetic regimens. The ED50 and ED95 neuromuscular blocking doses calculated from this single dose technique were 0.051 mg/kg and 0.095 mg/kg, respectively, in children anesthetized with halothane N2O:O2, and 0.059 mg/kg and 0.11 mg/kg in children anesthetized with N2O:O2 narcotic. The fourth subset of each group (A4 and B4) received 0.09 mg/kg and 0.11 mg/kg mivacurium, the estimated ED95 for each respectively. The last subsets (A5 and B5) received 0.2 mg/kg. This dose induced 100% depression of the twitch response in all 18 patients in 1.8 +/- 0.1 min, with recovery to 5%, 25%, and 95% of control occurring in 8.4 +/- 0.5, 11.2 +/- 0.6 and 18.4 +/- 1.6 min, respectively. The recovery indices for all patients were 4.6 +/- 0.6 min for 25-75% recovery and 9.7 +/- 1.3 min for 5-95% recovery.(ABSTRACT TRUNCATED AT 250 WORDS)     

Minimum Alveolar Concentration-Awake of Xenon Alone and in Combination with Isoflurane or Sevoflurane

Background: The minimum alveolar concentration (MAC)-awake is a traditional index of hypnotic potency of an inhalational anesthetic. The MAC-awake of xenon, an inert gas with anesthetic properties (MAC = 71%), has not been determined. It is also unknown how xenon interacts with isoflurane or sevoflurane on the MAC-awake.

Methods: In the first part of the study, 90 female patients received xenon, nitrous oxide (N2O), isoflurane, or sevoflurane supplemented with epidural anesthesia (n = 36 for xenon and n = 18 per group for other anesthetics). In the second part, 72 additional patients received either xenon or N2O combined with the 0.5 times MAC-awake concentration of isoflurane or sevoflurane (0.2% and 0.3%, respectively, based on the results of the first part; n = 18 per group). During emergence, the concentration of an assigned anesthetic (xenon or N2O only in the second part) was decreased in 0.1 MAC decrements every 15 min from 0.8 MAC or from 70% in the case of N2O until the patient followed the command to either open her eyes or to squeeze and release the investigator's hand. The concentration midway between the value permitting the first response to command and that just preventing it was defined as the MAC-awake.

Results: The MAC-awake were as follows: xenon, 32.6 +/- 6.1% (mean +/- SD) or 0.46 +/- 0.09 MAC; N2O, 63.3 +/- 7.1% (0.61 +/- 0.07 MAC); isoflurane, 0.40 +/- 0.07% (0.35 +/- 0.06 MAC); and sevoflurane, 0.59 +/- 0.10% (0.35 +/- 0.06 MAC). Addition of the 0.5 MAC-awake concentrations of isoflurane and sevoflurane reduced the MAC-awake of xenon to 0.50 +/- 0.15 and 0.51 +/- 0.16 times its MAC-awake as a sole agent, but that of N2O to the values significantly greater than 0.5 times its MAC-awake as a sole agent (0.68 +/- 0.12 and 0.66 +/- 0.14 times MAC-awake;P < 0.01, analysis of variance and Dunnett's test).